Skin disorders, such as acne, can be irritating and embarrassing. The major disease of skin associated with sebaceous follicles, is acne vulgaris. This is also the most common reason for visiting a dermatologist in the United States. There are many treatments, but no cures for acne. These include antibiotics (which inhibit growth of p. acnes bacteria which play a role in acne), retinoids such as Accutane(copyright) (isotetinoin, which reduces sebaceous gland output of sebum), and antimicrobials such as benzoyl peroxide. Acne lesions result from the rupture of a sebaceous follicle, followed by inflammation and pus (a xe2x80x9cwhiteheadxe2x80x9d), or by accumulation of plugged material in the sebaceous follicle (a xe2x80x9cblackheadxe2x80x9d). This pathophysiology has two major requirements: (1) plugging of the upper portion of the follicle, and (2) an increase in sebum production. The upper portion of the follicle, i.e., the xe2x80x9cporexe2x80x9d into which sebum is secreted and which is directly in communication with the skin surface, is called the infundibulum. A plug forms in the infundibulum from cells, sebum, bacteria, and other debris. The sebaceous gland continues to produce sebum (an oily fluid), stretching the infundibulum until either it or some lower portion of the follicles ruptures.
Generally, only a minority of sebaceous hair follicles on the face and upper back develop acne lesions. Therefore, it is likely that some structural differentiation predisposes a fraction of the follicles to develop acne. In most males, acne is worst in the teenage years and then subsides, suggesting that a subpopulation of follicles may be present which ultimately self-destruct. In women, teenage acne is often followed by menstrual acne flares well into adulthood. Since both plugging of the infundibulum and high sebaceous gland activity are necessary for an acne lesion to develop, it is likely that the predisposing factors for the follicles which become infected are (1) an infundibulum shape which is easily plugged, and/or (2) a hyperactive sebaceous gland.
Unlike medical dermatology, most laser dermatology treatments are actually xe2x80x9ccuresxe2x80x9dxe2x80x94producing a permanent anatomic, microsurgical effect on the skin. This includes skin resurfacing, portwine stain treatment, tattoo and pigmented lesion removal, and hair removal. Selective photothermolysis or controlled skin ablation with lasers or other extremely intense light sources, might therefore be capable of curing skin disorders, such as acne, if appropriately targeted to the primary site(s) of pathophysiology.
The present invention is based, at least in part, on the discovery that energy activatable materials, such as chromophores, described infra, in combination with an energy source, e.g., photo (light) therapy, can be used to treat sebaceous gland disorders, e.g., eliminate, inhibit, or prevent occurrence or reoccurrence of the skin disorder. A preferred example of such a sebaceous gland disorder is acne.
The present invention pertains to methods for treating skin disorders associated with sebaceous follicles by topically applying an energy activatable material to a section of skin afflicted with a sebaceous gland disorder, wherein the material is activated by energy which penetrates outer layers of epidermis. A sufficient amount of the material infiltrates the afflicted section of skin and is exposed to sufficient energy to cause the material to become photochemically or photothermally activated, thereby treating the sebaceous gland disorder. In one embodiment, the sebaceous gland disorder is acne. Suitable energy sources include flash lamp based sources and lasers, such as Nd: YAG, Alexandrite, flash lamp-pumped dyes and diodes. Alternatively, the energy source can also be a continuous wave energy source. In preferred embodiments, the energy activatable material is a laser sensitive chromophore, e.g., a chromophore which is capable of being photostimulated by a laser, e.g., a dye. In a particularly preferred embodiment, the chromophore is methylene blue.
The present invention also pertains to methods for modifying the opening to the infundibulum by topically applying an energy activatable material to the opening to the infundibulum, wherein the material is activated by energy which penetrates outer layers of epidermis. Preferably, the perfusion of the material into the pore opening and/or sebaceous gland is increased by iontophoresis. A sufficient amount of the material infiltrates spaces about the infundibulum and the infundibulum is exposed to sufficient energy to cause the material to become photochemically or photothermally activated, thereby modifying the opening to the infundibulum. In one embodiment, the opening to the infundibulum is enlarged. In another embodiment, the opening to the infundibulum is decreased. In still another embodiment, the opening to the infundibulum is altered such that pore pluggage will not occur, e.g., the infundibulum is reshaped such that excess sebum, oils, dirt and bacteria will not cause pore pluggage to occur, resulting in a black head (comedon) or white head (milium).
The present invention also pertains to methods for down regulating, e.g., decreasing, the oil/lipid output production of the sebaceous gland. Application of the energy activatable material to the pilosebaceous unit, e.g., the sebaceous gland, followed by stimulation by an energy source can cause selective permanent physical alteration to the sebaceous gland and/or follicle such that surrounding tissue remains unaffected. The physical alteration to the sebaceous gland and/or follicle results in diminished production of sebum.
The present invention further pertains to methods for modifying the pilosebaceous unit by topically applying an energy activatable material to the pilosebaceous unit, wherein the material is activated by energy which penetrates into the dermis and into the outer layers of epidermis. A sufficient amount of the material infiltrates the pilosebaceous unit and the pilosebaceous unit is exposed to sufficient energy to cause the material to become photochemically or photothermally activated, thereby modifying the pilosebaceous unit. In one embodiment, the pilosebaceous unit is treated such that sebum production is diminished. A decrease in pore pluggage can occur, as a result of the diminishment of sebum production. In one preferred embodiment, treatment of the pilosebaceous unit by the present invention results in elimination of pore pluggage, e.g., the pilosebaceous unit is treated such that excess sebum, oils, dirt and bacteria will not cause pore pluggage to occur, resulting in a black or white head.